Fluorine atom has high polarity and hydrophobic property, and has almost the same size as hydrogen atom. Such organofluoro compounds containing fluorine atoms have unique chemical and physiological properties compared to general organic compounds, and are usefully utilized in the area of medicine, agrochemical, dyestuff, polymer, and the like [Gerstenberger, M. R. C.; Haas, A. Angew. Chem., Int. Ed. Engl. 1981, 20, 647; Filler, R. In Organofluorine Compounds in Medicinal Chemistry and Biomedical Applications; Filler, R., Ed., Studies in Organic Chemistry 48, Elsevier, New York, N.Y., 1993, p 1-23].
Generally organofluoro compounds are prepared from the substitution reaction of fluoride by reacting alkyl halide or alkyl sulfonate with fluorine salt as shown in Chemical Equation 1.

Halide in alkyl halide is selected from the group consisting of Cl, Br, and I except F. Sulfonate in alkyl sulfonate is SO3R12 wherein R12 is alkyl or aryl group. The alkyl is preferably C1˜C12 alkyl halide or C1˜C12 alkyl sulfonate. For example, the alkyl sulfonate is selected from the group consisting of methane sulfonate, ethane sulfonate, isopropane sulfonate, chloromethane sulfonate, trifluoromethane sulfonate, and chloroethane sulfonate. Aryl group is preferably selected from the group consisting of phenyl, C1˜C4 alkyl phenyl, halo phenyl, C1˜C4 alkoxy phenyl, and nitro phenyl. Preferable examples are methylphenyl sulfonate, ethylphenyl sulfonate, chlorophenyl sulfonate, bromophenyl sulfonate, methoxylphenyl sulfonate, or nitrophenyl sulfonate.
Fluorine salt (MFn), as a source of fluoride, is selected from the group consisting of alkali metal fluoride containing alkali metals such as lithium, sodium, potassium, rubidium, or cesium; and alkaline earth metal fluoride containing alkaline earth metals such as magnesium, calcium, strontium, or barium; and ammonium fluorides containing ammonium or its derivative such as tetraalkylammonium.
Generally nucleophilic fluorination reaction is carried out in a polar aprotic solvent, such as acetonitrile (CH3CN), DMF, or DMSO, to increase the solubility of fluorine salt and the reactivity of fluoride. It is know that alcohol, a protic solvent, is not suitable for the nucleophilic fluorination reaction. It is further known that alcohol forms hydrogen bonds with fluoride which is a source of fluorine and thereby reduce reactivity in nucleophilic fluorination reaction [Smith, M. D.; March, J. Advanced Organic Chemistry, 5th ed.; Wiley Interscience: New York, N.Y., 2001; pp 389-674].
In the method for preparation of the above organofluoro compounds, it has been reported that alkyl fluoride is prepared by reacting potassium fluoride with alkyl halide in ethylene glycol solvent [Hoffmann, F. W. J. Am. Chem. Soc., 1948, 70, 2596]. However, this preparation method has disadvantages of low yield and long reaction time at high reaction temperature above 140° C., because reactivity is low due to the low solubility of potassium fluoride.
It has been reported that 18-crown-6 ether, which has strong bonds with metal ions, was used as a catalyst to prepare organofluoro compounds to increase the solubility of fluorine salt and the reactivity of fluoride, under relatively low temperature of 80˜90° C. and mild reaction conditions, and the yield of the product was high [Liotta, C. L.; Harris, H. P. J. Am. Chem. Soc., 1974, 96, 2250]. However, this process has disadvantages that 18-crown-6 ether is expensive, long reaction time is required and a large amount of alkene is produced as a side product because fluoride acts as base.
It is known that a side reaction, as shown in Chemical Equation 2, is accompanied when fluorine salt is used in the preparation of organofluoro compounds.

As an example, it is reported that tetrabutylammonium fluoride is used as a fluorine salt to prepare organofluoro compounds in high yield under mild reaction conditions [Cox, D. P.; Terpinsky, J.; Lawrynowicz, W. J. Org. Chem. 1984, 49, 3216.]. However, tetrabutylammonium fluoride hydrate has a problem that a large amount of alcohol, which is a side product caused by water, is produced, and alkene is produced as another side product due to the high basicity of tetrabutylammonium fluoride.
Therefore, for the preparation of organofluoro compounds by the reaction of fluorine salt with alkyl halide or alkyl sulfonate, a preparation method which may reduce the reaction time by increasing the reactivity of fluorine slat, and may reduce the formation of side products such as alkene and alcohol by eliminating the influence of moisture and minimizing basicity of fluoride itself is required.
The inventors have tried to solve the above problems. In the method for preparation of organofluoro compounds by reacting alkyl halide or alkyl sulfonate with fluorine salt, the inventors have found that the present invention is considered to follow the reaction shown in FIG. 1, but is not always limited thereto theoretically. The inventors have found that alcohol solvent increases nucleophilic substitution reactivity of fluorine salt by weakening ionic bonds of fluoride between metal cations and fluorine anions through hydrogen bonds with fluorine metal salts, and side reactions due to the influence of basicity is suppressed in fluorination reaction by weakening the basicity of fluoride through hydrogen bonds of fluoride, and the present invention has been completed.